Effect of increased dietary calcium on body weight, food and water intake in oral contraceptive treated female rats

The effects of high calcium diet on body weight in OC treated rats are unknown. This study therefore investigated the effect of increasing dietary calcium from 0.9% to 2.5% on body weight, food ingestion, water intake, heart weight index and renal weight index in female Sprague-Dawley rats treated with a combination of OC steroids (ethinyloestradiol + norgestrel). The rats were assigned into three groups of average of 11 rats each; control, OC-treated and OC + Calcium – treated groups and administered orally for 10 weeks. Food and water intake, body weight, cardiac weight index, left ventricular weight index, renal weight index and serum calcium level were determined. The result shows that OC treated rats had significantly lower serum calcium concentration, body weight gain, food, water and calcium intake than those of the control rats. The OC + Calcium – treated rat had significantly higher serum calcium concentration, food, water and calcium intake but significantly lower body weight than those of the OC - treated rats. OC + Calcium - treated rats had significantly higher water intake, calcium intake and significantly lower body weight and food intake when compared with the control rats. Cardiac weight index and renal weight index was comparable in all groups. In conclusion, combined OC-induced reduction in weight gain might be associated with inhibition of the feeding center and consequent inhibition of the thirst center. Co-administration of dietary calcium augmented the reduction in weight gain seen in OC-treated rats probably by further suppression of the feeding and thirst centers.     

下丘脑室旁核胃动素对消化功能影响的研究

目的:研究下丘脑室旁核注入胃动素及其拮抗剂对大鼠消化功能和体重增长的研究。方法:将剂量为0.005-5nmol的motilin和GM109注入大鼠下丘脑室旁核,1小时后可观察到大鼠摄食量显著增加并持续到两小时后。进食量的计算是通过预先称量好的鼠粮和应用药物20分钟、1小时、两小时后剩余数量比较而得出。实验持续一周。将实验组和对照组的进食量和体重进行比较。结果:室旁核注入胃动素5nmol的实验组和合并应用GM1090.005nmol的实验组在应用药物后1小时和2小时,可观察到摄食量显著增加(p<0.01),一周后体重也增加(p>0.05),然而摄食量的增加有显著性差异,体重的增加并无显著性差异。其他实验组也没有观察到显著性差异。结论:胃动素有调节消化运动,促进胃肠排空,促进食欲的作用。可能由于胃肠排空是频繁的,没有充裕的时间消化吸收,从而体重增加无显著性差异。     

下丘脑室旁核胃动素对消化功能影响的研究

目的：研究下丘脑室旁核注入胃动素及其拮抗剂对大鼠消化功能和体重增长的研究。方法：将剂量为0.005-5nmol的motilin和GM109注入大鼠下丘脑室旁核,1小时后可观察到大鼠摄食量显著增加并持续到两小时后。进食量的计算是通过预先称量好的鼠粮和应用药物20分钟、1小时、两小时后剩余数量比较而得出。实验持续一周。将实验组和对照组的进食量和体重进行比较。结果：室旁核注入胃动素5nmol的实验组和合并应用GM1090.005nmol的实验组在应用药物后1小时和2小时,可观察到摄食量显著增加（p〈0.01）,一周后体重也增加（p〉0.05）,然而摄食量的增加有显著性差异,体重的增加并无显著性差异。其他实验组也没有观察到显著性差异。结论：胃动素有调节消化运动,促进胃肠排空,促进食欲的作用。可能由于胃肠排空是频繁的,没有充裕的时间消化吸收,从而体重增加无显著性差异。     

Continuous intraventricular infusion of neuropeptide Y evokes episodic food intake in satiated female rats: effects of adrenalectomy and cholecystokinin

In these studies the pattern of feeding behavior during continuous intraventricular (IVT) infusion of NPY for 4 hr in the satiated female rat was monitored. Whereas saline infusion was ineffective, each of the three doses of NPY (117, 470 or 1175 pmol/hr) increased feeding during the entire 4 hr infusion and 2 hr postinfusion period. The cumulative food intake at the end of 4 hr of NPY infusion was enhanced in a dose-related fashion between 0, 117 and 470 pmol/hr; at 1175 pmol/hr food intake plateaued. In addition, the latency to initiate feeding response decreased in a dose-related fashion and feeding occurred in discrete (35-45) episodes during the 4 hr infusion period. Further, the total time feeding and local eating rate (g/min) increased significantly in response to the higher rates of NPY infusion. Concurrent infusion of cholecystokinin (CCK) at either equimolar or 2.5 x NPY dose, affected neither the NPY-induced cumulative food intake nor any other parameter of feeding behavior. On the other hand, cumulative food intake was significantly decreased in adrenalectomized rats in response to NPY infusion (470 pmol/hr); a response due primarily to a marked suppression in some, and almost complete cessation of food consumption in other rats during the second 2 hr period of NPY infusion. These studies show that continuous central infusion of NPY can produce sustained, intermittent feeding behavior and adrenalectomy significantly curtailed the duration of NPY effectiveness.(ABSTRACT TRUNCATED AT 250 WORDS)     

The effects of chronic central administration of corticotropin-releasing factor on food intake, body weight, and hypothalamic-pituitary-adrenocortical hormones.

The effects of chronic central administration of corticotropin-releasing factor (CRF) on food intake, body weight, and hypothalamic-pituitary-adrenocortical hormones were investigated in rats. The infusion of ovine CRF at doses of 0.3 and 1.0 microgram/h continuously induced decrease in food intake and a suppression of body-weight gain for 7 days. The inhibition of body weight gain induced by CRF could not be accounted for solely by a decreased food intake since the suppression of body-weight gain in CRF-infused rats was significantly greater than that observed in rats which received the same amount of food as the CRF-infused rats. The content of proopiomelanocortin (POMC) -derived peptides in the anterior lobe of the pituitary as well as the plasma levels of ACTH and corticosterone (B) were significantly elevated in CRF-treated rats, and the CRF content in the hypothalamus was significantly decreased. These results suggest that chronic intracerebroventricular (icv) administration of CRF stimulates the synthesis and secretion of POMC-related peptides in the pituitary and suppresses food intake accompanied by inhibition of body weight gain. The results are similar to clinical and laboratory findings observed in patients with stress-induced anorexia.     

Orexin-A受体介导的生长抑素激动剂ODT8-SST对大鼠摄食和饮水的影响

目的：探讨orexin-A（OXA）受体介导的生长抑素激动剂ODT8-SST 对大鼠摄食和饮水的调节作用相关作用机制。方法：在光 照周期内,大鼠40 只随机分8 组,侧脑室（icv）分别注射不同剂量ODT8-SST 或生理盐水（NS）;大鼠56 只随机分8 组分别侧脑 室注射不同剂量OXA 受体（OX1R）拮抗剂SB-334867 或NS;2小时后测量大鼠摄食量和饮水量。结果：与NS组相比,实验组大 鼠侧脑室注射ODT8-SST（1 ug/rat）,2 小时后摄食量和饮水量均显著增加（P<0.05）。大鼠侧脑室注射SB-334867（16 ug/rat）完全 抑制了由侧脑室注射ODT8-SST 后引起的摄食量和饮水量的增加;与此相反,大鼠给予SST2 拮抗剂S-406-028 预处理之后,可阻 止侧脑室注射ODT8-SST 引发的促进食欲作用,但不会影响侧脑室注射OXA（10.7 ug/rat）诱导的摄食量和饮水量的增加。结论： 侧脑室注射ODT8-SST 可促进摄食和饮水,该过程可能由OX1R所介导;orexin-A 促进摄食作用不依赖大脑SST2 通路的激活。     

Effect of chronic infusion of olanzapine and clozapine on food intake and body weight gain in male and female rats

Many antipsychotics cause weight gain in humans, but usually not in rats, when injected once or twice daily. Since blood antipsychotic half-lives are short in rats, compared to humans, chronic administration by constant infusion may be necessary to see consistent weight gain in rats. Male and female rats were implanted with mini-pumps for constant infusion of olanzapine (5 mg/kg/day), clozapine (10 mg/kg/day) or vehicle for 11 days. Food intake and body weight were measured; blood drug levels were measured by HPLC. Olanzapine increased food intake and body weight in female, but not male rats. Serum olanzapine concentrations were 30-35 ng/ml. Clozapine had no effect on food intake or body weight in female or male rats. Serum clozapine concentrations were about 75 ng/ml. Single-dose pharmacokinetic analysis revealed a serum terminal half-life of 1.2-1.5 h for each drug, with no sex differences. Despite the fact that olanzapine and clozapine promote weight gain in humans, these drugs appear to have minimal effects on body weight and food intake in rats, except for a modest effect of olanzapine in female rats, even though therapeutic levels of olanzapine are achieved in serum during chronic infusion. Hence, the rapid clearance of drug following single administration in previous studies cannot explain the weak or absent effects of antipsychotics on weight gain in this species. The rat thus appears to be an inadequate model of weight gain produced by some antipsychotics in humans.     

Strain differences in the dose-response curves of adrenalectomized, starved-refed rats to dehydroepiandrosterone (DHEA)

The effects of adrenalectomy and dehydroepiandrosterone (DHEA) doses (0, 15, 30, 60, 120 and 240 mg/kg/day ip) on hepatic enzyme activity and lipid content and on the amount of epididymal fat pad lipid were studied in starved-refed BHE and Sprague-Dawley rats. BHE rats had significantly greater relative liver size, glucose-6-phosphate dehydrogenase (G6PD) and malic enzyme (ME) activities, and percentage liver lipid but less epididymal fat pad lipid than Sprague-Dawley rats. Adrenalectomized (ADX) rats consumed significantly less food, gained less weight per day, and had less lipid in their livers and fat pads than intact rats. As the level of DHEA increased from 0 to 240 mg/kg/day there was a significant linear decrease in average daily weight gain, food intake, G6PD activity, and percentage liver lipid. At the 15 mg/kg/day dose, G6PD activity was significantly reduced without reductions in the other parameters measured. At the 120 mg/kg/day dose, however, weight gain, food intake, G6PD activity, and percentage liver lipid were significantly lower than that of the controls. At this dose DHEA treatment reduced food intake by 17% whereas it diminished average daily weight gain and G6PD activity by 30 and 56%, respectively. The 240 mg/kg/day dose of DHEA significantly reduced food intake, weight gain, liver lipid, G6PD activity, and ME activity. Intact and ADX BHE rats reduced their G6PD activity and liver lipid more rapidly than Sprague-Dawley rats as the level of DHEA administered increased. ADX Sprague-Dawley rats receiving DHEA had greater liver lipid content and enzyme activity than their intact counterparts whereas the reverse situation was true in BHE rats. These data indicate that the effect of DHEA on body weight gain, food intake, and hepatic and peripheral adiposity are dependent on the strain of rat, the adrenal status, and the DHEA dose.     

The effects of prior weight reduction on the running wheel-induced feeding suppression in rats

Adult male rats given ad lib access to food and a running wheel show an initial feeding and weight suppression. Over 6-10 days feeding recovers, but body weight remains low. It is not clear which effect is primary, the wheel-induced feeding or weight change. To test this, rats were first restricted to 15 g of food a day for 8 or 16 days to reduce their weight relative to control non-restricted rats. They were then returned to ad lib feeding and half the restricted and non-restricted control rats were introduced to the wheel either immediately (Experiment 1) or 4 days later (Experiment 2). Food intake, body weight, and wheel running were monitored throughout the experiments. At the return to ad lib feeding, prior food restriction elevated feeding. Both immediate and delayed wheel access suppressed feeding in both groups of wheel access rats compared to the appropriate control rats. Feeding history did not have a significant effect on wheel running. The wheel-induced reductions in feeding from baseline were similar in the weight reduced and normal weight animals suggesting that prior weight restriction did not prevent the onset of the wheel-induced feeding suppression. It is therefore suggested that the feeding suppression is not driven by a reduced weight set point.     

GABAA receptors in nucleus accumbens shell mediate the hyperphagia and weight gain following haloperidol treatment in rats

AimsWeight gain is a common outcome of antipsychotics therapy in schizophrenic patients. However, the underlying neuronal mechanisms are unclear. The present study was undertaken to investigate the role of GABA_A receptors within the framework of nucleus accumbens shell (AcbSh) in haloperidol-induced hyperphagia and body weight gain in sated rats.Main methodsIn acute studies, GABA_A receptor agonists muscimol, diazepam or antagonist bicuculline were administered by AcbSh route, alone or in combination with haloperidol (intraperitoneal/ip). Immediately after these treatments, preweighed food was offered to the animals at commencement of dark phase. Cumulative food intake was measured at 2 and 6 h post-injection time-points. Furthermore, effects of subacute haloperidol treatment, alone or in combination with muscimol, diazepam or bicuculline, on food intake and body weight were investigated.Key findingsWhile acute treatment with haloperidol, muscimol or diazepam dose dependently stimulated the food intake, bicuculline suppressed the same. Prior administration of muscimol (20 ng/rat, intra-AcbSh) and diazepam (5 µg/rat, intra-AcbSh) significantly potentiated, whereas bicuculline (40 ng/rat, intra-AcbSh) negated the hyperphagic effect of acute haloperidol (0.005 or 0.01 mg/kg/rat, ip). Subacute administration of haloperidol (0.01 mg/kg/rat/day, ip) for 15 days produced increase in food intake and body weight. Although, concomitant administration of muscimol (20 ng/rat/day, intra-AcbSh) or diazepam (5 μg/rat/day, intra-AcbSh) markedly enhanced, bicuculline (40 ng/rat/day, intra-AcbSh) prevented the subacute haloperidol-induced hyperphagia and weight gain.SignificanceThe results of present study suggest that increased food intake and body weight following haloperidol treatment in rats, may be mediated via AcbSh GABA_A receptors.     

Chronic injection of pansomatostatin agonist ODT8-SST differentially modulates food intake and decreases body weight gain in lean and diet-induced obese rats

The aim of this study was to investigate the central actions of the stable pansomatostatin peptide agonist, ODT8-SST on body weight. ODT8-SST or vehicle was acutely (1μg/rat) injected or chronically infused (5μg/rat/d, 14d) intracerebroventricularly and daily food intake, body weight and composition were monitored. In lean rats, neither acute nor chronic ODT8-SST influenced daily food intake while body weight was reduced by 2.2% after acute injection and there was a 14g reduction of body weight gain after 14d compared to vehicle (p<0.01). In diet-induced obese (DIO) rats, chronic ODT8-SST increased cumulative 2-week food intake compared to vehicle (+14%, p<0.05) and also blunted body weight change (-11g, p<0.05). ODT8-SST for 14d reduced lean mass (-22g and -25g respectively, p<0.001) and total water (-19g and -22g respectively, p<0.001) in lean and DIO rats and increased fat mass in DIO (+16g, p<0.001) but not lean rats (+1g, p>0.05) compared to vehicle. In DIO rats, ODT8-SST reduced ambulatory (-27%/24h, p<0.05) and fine movements (-38%, p<0.01) which was associated with an increased positive energy balance compared to vehicle (+50g, p<0.01). Chronic central somatostatin receptor activation in lean rats reduces body weight gain and lean mass independently of food intake which is likely related to growth hormone inhibition. In DIO rats, ODT8-SST reduces lean mass but promotes food intake and fat mass, indicating differential responsiveness to somatostatin under obese conditions.     

Leptin-derived peptides that stimulate food intake and increase body weight following peripheral administration

We previously showed that peptides containing leptin sequences 1-33 or 61-90 are taken up by the rat brain. We now report the effects of these peptides on food intake and body weight in mature rats. Peptides were infused intravenously for 4weeks, using Alzet minipumps. Dosages were 20μg/kg/day in experiment I, and 60μg/kg/day in experiment 2. In experiment 1, female rats receiving peptides 1-33 and 61-90 each underwent an approximate doubling of the weight gain of control rats. These peptides also increased food intake in female rats. Peptide 15-32, which has a lesser degree of brain uptake, gave a smaller weight gain. Peptide 83-108, which is not taken up by the brain, had no effect on weight gain or food intake. Similar results were obtained in experiment 2. In male rats, however, none of the peptides caused significant changes in food intake or body weight. This was at least partly due to the fact that all male rats underwent vigorous weight increases. We conclude that peptides 1-33 and 61-90 acted as leptin antagonists, stimulating food intake and body weight increases, at least in female rats. These peptides may lead to clinical applications in conditions such as anorexia and cachexia.     

Feeding and temperature responses to intravenous leptin infusion are differential predictors of obesity in rats

Obesity is frequently associated with leptin resistance. The present study investigated whether leptin resistance in rats is present before obesity develops, and thus could underlie obesity induced by 16 wk exposure to a liquid, palatable, high-energy diet (HED). Before HED exposure, male Wistar rats (weighing between 330 and 360 g) received intravenous infusions of 20 microg leptin 2 h before dark (approximately 57 microg/kg rat). Relative to saline infusion, this caused a highly variable effect on food intake (ranging between -94 and +129%), with food intake suppression that appeared negatively correlated with HED-induced increases in body weight gain, caloric intake, adiposity, and plasma leptin levels. In contrast, leptin's thermogenic response was positively correlated to body weight gain linked to weights of viscera, but not to adiposity. Before HED exposure, leptin unexpectedly increased food intake in some rats (fi+, n = 8), whereas others displayed the normal reduction in food intake (fi-, n = 7). HED-exposed fi+ rats had higher plasma leptin levels, retroperitoneal fat pad weight, HED intake, and body weight gain than fi- and chow-fed rats. These parameters were also higher in HED-exposed fi-rats relative to chow rats, except for plasma leptin concentrations. It is concluded that leptin's reduced efficacy to suppress food intake could predict obesity on an HED. An unexpected orexigenic effect of leptin might potentially contribute to this as well.     

Paraventricular nucleus injections of peptide YY and neuropeptide Y preferentially enhance carbohydrate ingestion

Neuropeptide Y (NPY) injected into the paraventricular nucleus (PVN) is known to elicit a powerful feeding response in satiated, brain-cannulated rats [41, 42, 43]. The present experiment investigates the effect of peptide YY (PYY), a structurally-related peptide, on feeding behavior and, in addition, the effects of both PYY and NPY on the pattern of macronutrient selection. Injection of PYY directly into the PVN, in doses ranging from 7.8 to 235 pmol/0.3 μl, caused a strong, dose-dependent stimulation of feeding behavior, as well as a small stimulation of drinking behavior, in satiated rats. The mean latency to eat was 9.3 min, with substantial feeding occurring within 30 min of the injection. At low doses, the increase in feeding was seen predominantly during the first hr. At the highest dose, in contrast, food intake continued to increase progressively over the next few hr, such that by 4 hr postinjection food intake was more than 20 g over vehicle baseline. In 1 hr tests with 3 pure macronutrient (protein, fat and carbohydrate) diets simulataneously available, PYY and NPY (78 pmol/0.3 μl) both elicited a strong and selective increase in carbohydrate consumption, with little or no effect on protein or fat consumption. These results suggest that hypothalamic receptors sensitive to PYY and NPY may participate in the control of carbohydrate consumption.     

Suppression of food intake and body weight gain by naloxone in rats

The effect of acute and chronic administration of naloxone on food acquisition and weight gain in rats was studied in 3 experiments. One injection of a sparingly-soluble salt of naloxone in slow-release vehicle markedly lowered mean food intake over that of control rats injected with the vehicle only. Mean body weight of the naloxone-injected rats was significantly lower than that of the control group for one week.Repeated evening injections (2000 h) of naloxone hydrochloride in saline tended to reduce the night-time feeding below control levels throughout the 10-day period of naloxone administration. Food intake was significantly lower in the 4- and 8-h periods after the first injection of naloxone than that on the preceding saline control night. The initial decreases were offset by increased day-time feeding so that total daily food intake was not significantly altered over the 10 days. When saline was substituted for naloxone, food intake increased.Rats given naloxone following 24 h of fasting consumed significantly less food and gained less weight during 4 h of access to food compared to those receiving saline. After a 48-h fast naloxone-treated rats also gained significantly less body weight than those given saline, but the reduction in food intake was not statistically significant. These results suggest the possibility that endorphins may have a modulating effect on feeding activity.     

Effects of naloxone and cholecystokinin on food and water intake in vasopressin-deficient rats (Brattleboro strain)

Opioid peptides and cholecystokinin (CCK) have been shown to play a role in regulation of feeding behavior. Another neuropeptide that has recently been suggested to be involved in feeding is vasopressin. We explored possible interactions between opiates, CCK and vasopressin in feeding regulation by studying feeding suppression produced by naloxone and CCK in Brattleboro (DI) rats, which are homozygous for diabetes insipidus and lack the ability to synthesize vasopressin. Ten DI and 15 age-matched Long Evans (LE) rats were food deprived for 14 hours on two different days and then injected with naloxone (2.5 mg/kg) on one day or saline on the other. Thirty minutes later the food was returned and food and water consumption were measured after 1, 3 and 4 hr. Naloxone suppressed the food consumption of both DI and LE rats but the suppression was greater for the DI rats. This result was specific to feeding as water consumption was suppressed in LE more than in DI rats. Two weeks later, the same rats were food deprived for 6 hours on two different days and then injected with CCK-8 (2.5 micrograms/kg) on one day and with saline on the other. Food was returned one minute after the injection and food and water consumption were measured 30 and 60 minutes later. Food intake was reduced equally for both DI and LE rats. Water intake was not reduced. The results suggest that the suppression of feeding by CCK does not require an intact vasopressinergic system. The greater feeding suppression by naloxone in DI rats may suggest that opiates are interacting with vasopressin in producing their effects on food intake.     

Cyclic estradiol treatment normalizes body weight and restores physiological patterns of spontaneous feeding and sexual receptivity in ovariectomized rats

Hypothalamic-pituitary-gonadal axis function strongly influences feeding and body weight in cycling females in many species. To test the sufficiency of cyclic variations in plasma estradiol to reproduce normal patterns of spontaneous feeding, food intake, and body weight, ovariectomized Long-Evans rats were subcutaneously injected every fourth day with 2 microg estradiol benzoate or with the oil vehicle alone. Cyclic estradiol treatment completely normalized the trajectory of body weight gain and total food intake through seven treatment cycles. The hyperphagia of ovariectomized rats was expressed as an increase in spontaneous meal size. Meal frequency decreased, but not enough to compensate for the increase in meal size. Estradiol treatment normalized both parameters. In addition, cyclic estradiol treatment produced a further phasic decrease in meal size (and increase in meal frequency) and a decrease in food intake during the second night after injection. This phasic change is similar to the feeding changes occurring during estrus in intact rats. Sexual receptivity was measured during the eighth estradiol treatment cycle, 4 h after injection of 0.5 mg progesterone. Lordosis scores at the time of the treatment cycle modeling estrus were maximal, and scores at the time modeling diestrus were slightly increased over those of rats that did not receive estradiol. Finally, plasma estradiol levels, measured during the ninth treatment cycle, revealed a near-normal cyclic pattern of plasma estradiol levels. These results provide the first demonstration that the induction of a cyclic, near-physiological pattern of plasma estradiol is sufficient to maintain normal levels of body weight, spontaneous feeding patterns, total food intake, and (together with progesterone) sexual receptivity in ovariectomized rats.     

The effect of acarbose on the food intake, weight gain, and adiposity of LA/N-cp rats.

1. Groups of lean and obese LA/N-cp rats were administered the intestinal glucosidase inhibitor acarbose at 150 or 300 mg/kg diet from 7 until 17 weeks of age and the effects of the drug on food intake patterns and adiposity determined. 2. Dose related effects on body weights, adiposity and feed efficiency ratio were observed (control greater than 150 mg greater than 300 mg drug/kg diet) following treatment in both phenotypes, with the greatest differences observed in the obese phenotype. 3. Acarbose at both dosages was associated with phenotype-specific alterations in food intake amount and feeding pattern, resulting in an attenuation of age-associated increases in food intake. The feed efficiency ratio decreased in both phenotypes, and approached normally fed lean controls in obese rats administered the greater dosage. 4. These results indicate that patterns of food intake and weight gain differ markedly between lean and obese rats of this strain, and acarbose brings about a dose-related attenuation of developing food intake patterns in both phenotypes and which are associated with decreases in weight gain and adiposity. Thus, this drug may have therapeutic potential as an adjunct agent in the treatment of obesity and/or other disorders of carbohydrate intolerance.     

Combined stimulation of glucagon-like peptide-1 receptor and inhibition of cannabinoid CB1 receptor act synergistically to reduce food intake and body weight in the rat

Pharmacological activation of the glucagon-like peptide-1 (GLP-1) receptor and inhibition of the cannabinoid CB1 receptor were found to reduce food intake and body weight in humans and animals. Since earlier studies revealed that endocannabinoids may interact with other neurotransmitters to affect feeding behavior, we have examined whether a stable GLP-1 agonist, exendin-4 and a CB1 receptor antagonist, AM 251, may reciprocally enhance their inhibitory effects on food consumption in the rat. Additionally, we have tested whether the blockade of the GLP-1 receptor by exendin (9-39) modifies AM 251-dependent effects on energy balance. In a dose-response study, male Wistar rats were injected intraperitoneally with either 1.5-6.0 μg/kg exendin-4, 0.5-2 mg/kg AM 251, 80-320 μg/kg exendin (9-39) or their vehicle and the daily food and water intake as well as body weight changes were monitored two days before and two days after the injection. Exendin-4 at a dose of 3.0 and 6.0 μg/kg and AM 251 at a dose 2 mg/kg decreased significantly 24-hour food intake and body weight. Therefore, in the next study, the effects of lower doses of exendin-4 (1.5 μg/kg) and AM 251 (1.0 mg/kg) administered alone or together on food consumption were compared. As opposed to being injected alone, the co-administration of the two resulted in a marked decrease in both daily food intake and body weight. Exendin (9-39) did not modify the suppressory effect of the highest AM 251 dose on food consumption. Apparently, the effect of AM 251 on the appetite is not mediated by GLP-1. The concomitant stimulation of GLP-1 receptor and blockade of CB1 receptor, however, may act synergistically to inhibit appetite in the rat.     

Does neuropeptide Y contribute to the anorectic action of amylin?

Neuropeptide Y (NPY) is a potent feeding stimulant acting at the level of the hypothalamus. Amylin, a peptide co-released with insulin from pancreatic beta cells, inhibits feeding following peripheral or central administration. However, the mechanism by which amylin exerts its anorectic effect is controversial. This study investigated the acute effect of amylin on food intake induced by NPY, and the effect of chronic amylin administration on food intake and body weight in male Sprague Dawley rats previously implanted with intracerebroventricular (icv) cannulae. Rats received 1 nmol NPY, followed by amylin (0.05, 0.1, 0.5 nmol) or 2 microl saline. Increasing doses of amylin resulted in a dose-dependent inhibition of NPY-induced feeding by 31%, 74% and 99%, respectively (P < 0.05). To determine the chronic effects of i.c.v. amylin administration on feeding, rats received 0.5 nmol amylin or saline daily, 30 min before dark phase, over 6 days. Amylin significantly reduced food intake at 1, 4, 16 and 24 hours; after 6 days, amylin-treated rats showed a significant reduction in body weight, having lost 17.3 +/- 6.1 g, while control animals gained 7.7 +/- 5.1 g (P < 0.05). Brain NPY concentrations were not elevated, despite the reduced food intake, suggesting amylin may regulate NPY production or release. Thus, amylin potently inhibits NPY-induced feeding and attenuates normal 24 hour food intake, leading to weight loss.